1. Field of the Invention
The present invention relates to a genetically modified animal for use in evaluating the harmfulness of test substances and a method for evaluating the action of test substances in the genetically modified animal or part thereof.
2. Description of the Related Art
There have been concerns about the effect of environmental pollutant chemicals such as dioxins, PCBs, brominated flame retardants, and some agricultural chemicals on human health. In addition, many of various chemicals used in industrial activity or everyday life may have an unknown effect on human health.
Such chemicals are considered to act on biological functions such as liver function, reproductive function, immune function, and neural function and to have a harmful effect on human health.
Therefore, techniques for detecting and/or evaluating a biological function on which a specific chemical substance can act are very important for definition of handling or control of chemicals or for treatment of a human exposed to chemicals. Particularly, in recent years, it has been pointed out that exposure to some chemicals during the fetal or infant period could cause infants to have autism or higher brain dysfunction such as hyperactivity disorder. Therefore, there has been a demand for the development of techniques to evaluate the effect of chemicals on the neural function.
Currently, techniques to evaluate the effect of chemicals on biological functions are broadly classified into in vitro evaluation techniques using single cells and in vivo evaluation techniques using animal individuals.
The in vitro evaluation techniques include a technique of using mouse liver-derived Hepalc1c7 cells to evaluate the effect of test substances on the liver function (U.S. Pat. No. 5,854,010) and a method of using human mammary gland-derived MCF-7 cells to evaluate the effect of test substances on the reproductive function (JP-A 2002-253231). As regards the neural function, an in vitro evaluation method using mouse Neuro2a neuroblastoma cells has already been reported by the present applicant. This method includes transfecting the cells with a reporter gene under the control of a promoter having an aryl hydrocarbon receptor-binding enhancer sequence for a tyrosine hydroxylase gene (TH) gene and a TH gene core promoter sequence to produce genetically modified cells and evaluating the effect of a test substance on the central nervous system in the genetically modified cells. Concerning the in vivo evaluation techniques, there have been reported methods for evaluating the effect of test substances on the reproductive function, which use genetically modified mice produced by the introduction of a reporter gene under the control of an Mvh gene or c-mos gene promoter (JP-A 2001-8577 and 2001-8578).